It has been proposed by Parkinson et al. in U.S. Pat. Nos. 4,190,716 and 4,298,595 to provide a pharmaceutical composition for the release of 5-aminosalicylic acid to the gastrointestinal tract, starting from a non-absorbable pharmacologically acceptable organic polymeric backbone, containing aromatic rings, to which are covalently bonded by azo bonds salicylic acid or salicylate salt groups. In one embodiment, polystyrene is nitrated, reduced, diazotized and coupled with salicylic acid.
In British Pat. No. 993,961, the covalent linking of immunologically active materials, such as peptides, to polystyrene has been disclosed.
Rimington et al. (U.S. Pat. No. 3,862,312) have proposed compositions comprising acid addition salts of dl-tetramisole and a sulfonated polystyrene resin. Irmscher et al. (U.S. Pat. No. 3,780,171) have proposed ingestible polymeric compositions, in which active compounds are bound to amino-substituted polystyrenes.
Bauman et al. (U.S. Pat. No. 3,484,390) recite the formation of a diazotizable amino-function to a modified cellulosic backbone. The resulting product is a chelating resin.
Heyna et al. (U.S. Pat. No. 2,784,204) have proposed a vinylic monomer, comprising diphenylamine-vinylsulfone, which may contain azo functions and be used in dye chemistry. Furia (U.S. Pat. No. 3,976,797) indicates that polymeric azo colorants have properties, differing from those of monomeric azo colorants.
Lednicer et al. (U.S. Pat. No. 4,008,208) have proposed a pharmacologically active material, which contains azo linkages.
Peppercorn et al., J. Pharmacol. and Infect. Therap., vol 181 (1972) at 555, have described the role of intestinal bacteria in the metabolism of salicylazosulfapyridine and determined that intestinal bacteria cleave SAS to sulfapyridine and 5-aminosalicylate.
The question of the oral administration of peptides, particularly hormones, has been addressed by Saffran, Endocrinologica Experimentalis, vol. 16 (1982) at 327 and by Saffran et al., Can. J. Biochem., vol. 57 (1979) at 548. The use of biodegradable plastic pill coatings is considered a possible approach to solving the problem of degradation of orally-administered peptides.
It is an object of this invention to provide azo-containing polymeric materials, the azo bond of which can be degraded by chemical reduction in the large intestine of animals, including humans, to degrade the resin and permit release of medicaments to the animal. Alternatively, the resins can incorporate a medicament, which is released by reduction of the azo bonds.